Gemcitabine/cisplatin (GC) combination therapy has been the standard palliative chemotherapy for patients with advanced biliary tract cancer (BTC). No randomized clinical trials have been able to demonstrate the survival benefit over GC during the past decade. In our previous phase II trial, adding S-1 to GC (GCS) showed promising efficacy and we aimed to determine whether GCS could improve overall survival compared with GC for patients with advanced BTC.We performed a mulitcenter, randomized phase III trial across 39 centers. Enrolled patients were randomly allocated (1:1) to either the GCS or GC arm. The GCS regimen comprised gemcitabine (1000 mg/m2 ) and cisplatin (25 mg/m2 ) infusion on day 1 and 80 mg/m2 of S-1 on days 1-7 every 2 weeks. The primary endpoint was overall survival (OS) and the secondary endpoints were progression-free survival (PFS), response rate (RR), and adverse events (AEs). This study is registered with Clinical trial identification: NCT02182778.Between July 2014 and February 2016, 246 patients were enrolled. The median OS and 1-year OS rate were 13.5 months and 59.4% in the GCS arm and 12.6 months and 53.7% in the GC arm, respectively (hazard ratio [HR] 0.79, 90% confidence interval [CI]: 0.628-0.996; P = .046 [stratified log-rank test]). Median PFS was 7.4 months in the GCS arm and 5.5 months in the GC arm (HR 0.75, 95% CI: 0.577-0.970; P = .015). RR was 41.5% in the GCS arm and 15.0% in the GC arm. Grade 3 or worse AEs did not show significant differences between the two arms.GCS is the first regimen which demonstrated survival benefits as well as higher RR over GC in a randomized phase III trial and could be the new first-line standard chemotherapy for advanced BTC. To exploit the advantage of its high RR, GCS is now tested in the neoadjuvant setting in a randomized phase III trial for potentially resectable BTC.
The optimal treatment for hepatocellular carcinoma (HCC) should be selected based on tumor conditions, liver functional reserve, and performance status. Surgical treatment, such as liver resection and liver transplantation, is the most favorable treatment method; however, its indication criteria differ according to each country’s guidelines. In Western countries, liver resection is indicated only for early-stage HCC patients with Barcelona-Clinic Liver Cancer staging classification (BCLC) 0/A. While in Asian countries, liver resection is one of the treatment options for advanced HCC, such as BCLC B/C. Recently, the treatment of HCC is about to enter a drastic transitional period. It started with the widespread use of minimally invasive surgery for HCC, followed by a high rate of hepatitis C virus eradication with the advent of direct acting antivirals and developing a multidisciplinary treatment for highly advanced HCC. As a result, the importance of liver resection for HCC is increasing, and it is time to reconsider the criteria for selecting treatment methods for HCC patients. This article outlines current topics in the surgical treatment of HCC.
We have proposed a non-invasive heating method using the resonant cavity applicator system for deep-seated brain tumors. In this study, the heating properties of a resonant cavity applicator using an agar phantom with the cooling effect of blood perfusion are described. Blood perfusion is an important factor to control the temperature distribution during hyperthermia treatments. The purpose of this study is to demonstrate the cooling effect around blood vessels with the resonant cavity applicator. First, we proposed a simple model made of an agar with a blood vessel. One tube made of Teflon material assumed to be blood vessel with water circulating through it was placed inside the agar phantom. Second, we heated the simple model using the developed resonant cavity applicator. From these heating results, it was found that cooling effects of blood perfusion appear within the heated area approximately 2 cm away from blood vessels.
e14507 Background: Biomarkers to predict the efficacy of immunotherapy have been awaited. A phase I/II study of five therapeutic epitope-peptides for advanced colorectal cancer (CRC) using five novel HLA-A*2402-binding peptides. We explored the predictive biomarker for the response to immunotherapy. Methods: Each of the five peptides(3mg) was mixed with IFA and subcutaneously administered weekly for 12 weeks and after then biweekly. In the phase II study, chemotherapy was performed simultaneously as mFOLFOX6 (n = 93) or XELOX (n = 3) with bevacizumab (n = 5). All enrolled pts had received the therapy without knowing HLA-A status double-blindly, and the HLA-A genotypes were key-opened at analysis point. Pretreatment serum IL-6, CRP, lymphocyte%, neutrophil/lymphocyte (N/L) ratio ,and expression profiles of miR of the tumor and stroma using laser capture microdissection were evaluated between HLA-A*2402 positive group and negative group. Results: IL-6 < 1.0 (pg/ml) and Lymphocyte% > 15% were the significant predictive markers (p = 0.007, 0.034) for the long survival, which was observed only in HLA-A*2402 positive group. In the patients with IL-6 < 1.0 or lymphocyte% > 15, obvious trend to long survival in HLA-A*2402 positive group was observed. miR-378a of cancer and miR-125b in stromal were confirmed for the predictive biomarkers. Patients with low miR-378a or low miR-125b were significantly survived longer than high miR groups which significances were observer only in HLA-A*2402 group. Conclusions: IL-6, Lymphocyte%, and miRs expression were the predictive biomarkers for the response to peptides vaccine and the selection of patients.
Case 1: A 64-year-old man with a chiefcomplaint ofbloody stools was seen in our hospital. He underwent an extended right lobe resection for hilar cholangiocarcinoma 3 years ago and was in the middle of chemotherapy for multiple metastases. Case 2: A 69-year-old man with a chiefcomplaint ofbloody emesis and stools was seen. He underwent left hepatic trisegmentectomy for hilar cholangiocarcinoma and ligation of the right portal vein for postoperative portal venous thrombus 6 months ago. After careful examination, the patients in both cases were diagnosed with bleeding of the jejunal varices formed at the site ofhepaticojejunostomy. The patient in Case 1 underwent percutaneous transhepatic obliteration ofvarices and the patient in Case 2 underwent transileocolic vein obliteration ofvarices. After hepatobiliary pancreatic surgery with biliary tract reconstruction, we should be aware of ectopic varices during differential diagnosis of gastrointestinal bleeding.
Background Accumulating evidence shows an over-abundance of Fusobacterium nucleatum in colorectal tumour tissues. Although stool DNA testing of Fusobacterium nucleatum might be a potential marker for the detection of colorectal tumours, the difficulty in detecting Fusobacterium nucleatum in stool by conventional methods prevented further explorations. Therefore, we developed a droplet digital polymerase chain reaction (PCR) assay for detecting Fusobacterium nucleatum in stool and investigated its clinical utility in the management of colorectal tumours in a Japanese population. Methods Feces were collected from 60 healthy subjects (control group) and from 11 patients with colorectal non-advanced adenomas (non-advanced adenoma group), 19 patients with colorectal advanced adenoma/carcinoma in situ (advanced adenoma/carcinoma in situ (CIS) group) and 158 patients with colorectal cancer of stages I to IV (colorectal cancer group). Absolute copy numbers of Fusobacterium nucleatum were measured by droplet digital PCR. Results The median copy number of Fusobacterium nucleatum was 17.5 in the control group, 311 in the non-advanced adenoma group, 122 in the advanced adenoma/CIS group, and 317 in the colorectal cancer group. In comparison with that in the control group, the Fusobacterium nucleatum level was significantly higher in the non-advanced adenoma group, the advanced adenoma/CIS group and the colorectal cancer group. Conclusions This study illustrates the potential of stool DNA testing of Fusobacterium nucleatum by droplet digital PCR to detect individuals with colorectal tumours in a Japanese population.
A 52-year-old man presented with a postoperative abdominal ultrasound of left renal cell carcinoma, which revealed a dilated main pancreatic duct in the pancreatic body tail. A 15 mm tumor was noted in the pancreatic head-neck region on CT, and was diagnosed as invasive pancreatic cancer on EUS-FNA. The tumor was diagnosed as resectable pancreatic head-body cancer, and after neoadjuvant chemotherapy, a subtotal stomach-preserving pancreaticoduodenectomy was performed. Postoperative histopathology showed well-differentiated adenocarcinoma, TS1(9 mm), T1bN0M0, Stage Ⅰ, preoperative chemotherapy efficacy was Grade 2, and R0 resection was obtained. At the same time, a 4 mm-sized nodule was found in the center of the pancreatic head, far from the primary pancreatic cancer, and was diagnosed as renal cell carcinoma intrapancreatic metastasis. He received 4 courses of S-1 therapy as postoperative adjuvant chemotherapy for pancreatic cancer, and is alive 23 months postoperatively without recurrence. The coexistence of primary pancreatic cancer and pancreatic metastasis of renal cell carcinoma is extremely rare, and we report this case with a review of the literature.
